A recent review commissioned by NCCAM concluded that the research on meditation practices is characterized by poor methodological quality and that more rigorous science is needed before firm conclusions can be drawn on the effectiveness of these practices for improving health and well-being. The best studied form of meditation is mindfulness, which is most commonly taught by the Mindfulness-Based Stress Reduction (MBSR) training developed by members of our research team at UMass. The immediate goal of the proposed R34 is to validate a proposed biomarker for the effects of MBSR. Based on our preliminary data, we propose that resting-state fMRI measurement of functional connectivity (FC) in the limbic stress response network will be a valuable biomarker for the effect of MBSR on emotional and stress reactivity and will predict sustained improvements in health behaviors. This biomarker will enable future large-scale randomized trials that focus on the effectiveness of MBSR for long-term health behavior change, such as maintenance of weight loss. The proposed biomarker will allow future studies to refine MBSR interventions based on improved understanding of the effective components and individual differences, reduce reliance on self-reported measures, and provide an objective measure for identifying patients most likely to benefit and those who may need a tailored intervention. Our Specific Aims are to: (1) Validate functional connectivity as a biomarker for responsiveness to MBSR; (2) Investigate the association of functional connectivity change with changes in health behaviors at 6 month follow-up. Our preliminary data demonstrate that FC in the amygdala-orbitofrontal circuit is 1) strongly correlated with trait mindfulness and inversely correlated with emotional reactivity, and 2) enhanced by just 8 weeks of MBSR training Moreover, MBSR produces quantifiable changes in this circuit that correspond to improvements in psychological traits shown to impact health behaviors. We will randomize 100 community participants to MBSR or an attention control. Endpoints include changes in FC, health behavior (sleep quality, physical activity, healthy eating), and related psychological constructs (perceived stress, depression, trait anxiety, and trait anger, and positive affect). Endpoints will be measured at baseline, 8 weeks and 12 weeks, with an additional measurement at 6 months for health behavior and psychological outcomes. We hypothesize that the intervention group will experience a greater increase in FC than the comparison group and that changes in FC will correlate with health behavior and psychological constructs. We will also account for intervention engagement and expectancy. The ability to objectively and quantitatively measure the effects of MBSR/mindfulness on the brain is highly innovative. Our inter-disciplinary research team includes the developer of MBSR, experienced clinical trials / behavioral therapy researchers, and experts in functional imaging methods.